Complete pathological remission is possible with systemic combination chemotherapy for inoperable hepatocellular carcinoma

The purpose of this Phase II study was to determine the response rate, the toxicity, and the effect on survival of the combination of cisplatin, doxor ubicin, 5-fluorouracil, and alpha-IFN (PIAF) in advanced unresectable hepat ocellular carcinoma. Fifty patients with either unresectable or metastatic disease were treated with PIAF: cisplatin (20 mg/m(2) i.v., days 1-4), doxo rubicin (40 mg/m(2) i.v., day 1), 5-fluorouracil (400 mg/m(2) i.v., days 1- 4), and (alpha-IFN (5 MU/m(2) s.c., days 1-4), Treatment was repeated every 3 weeks to a maximum of six cycles, All patients were evaluable for respon se, toxicity, and survival. As assessed by conventional imaging criteria, t here were no complete responses, but 13 patients (26%) had a partial respon se. Among the 36 patients who had an initially high alpha-fetoprotein level (>500 ng/ml), 15 (42%) had a >50% fall after therapy, Nine patients underw ent surgical resection after achieving partial response and, in 4 of these patients, histological examination of the resected specimens revealed no vi able tumor cells. All these nine patients are alive, and eight patients rem ain in complete remission at between 7.6 and 25.8 months at the time of ana lysis. The overall median survival was 8.9 months. Toxicity was mainly myel osuppression and mucositis, There were two treatment-related deaths due to neutropenic sepsis, PIAF is active in hepatocellular carcinoma despite cons iderable hematological toxicity. Complete pathological remission is possibl e with this systemic combination. Apparently, persistent radiological lesio ns may still represent complete pathological resolution of active disease.